Mendelian Randomization Studies on Actinic Keratosis

BACKGROUND/AIM: Actinic keratosis (AK) is a common skin condition associated with cumulative sun exposure and advancing age. As a precursor to squamous cell carcinoma, it is clinically relevant as a target for prevention. While epidemiological studies have suggested various risk factors, causal inference is often limited by confounding. Mendelian randomization (MR), which uses genetic variants as proxies for exposures, can help address this. This review aimed to provide an overview of published MR studies that have examined AK either as an exposure or an outcome. MATERIALS AND METHODS: We conducted a systematic literature search in MEDLINE and Embase from inception to August 2025. Eligible studies were original human research employing MR to investigate associations involving AK and any health-related trait. RESULTS: Eight studies were included, all of which applied two-sample MR using summary-level genome-wide association data, primarily from European populations. The studies explored a variety of exposures, including metabolic traits, immune cell characteristics, dermatological conditions, and sun sensitivity. One study examined AK as an exposure to assess its association with skin cancers. Most analyses were exploratory, and no exposure-outcome pair was studied in more than one paper, limiting conclusions and precluding meta-analysis. CONCLUSION: The body of MR research concerning AK is limited but methodologically diverse. Although the current evidence base is small, this review highlights how MR has been applied to AK and may inform directions for future investigation.